Ultrasonography of liver tumors involves two stages: detection and characterization.
Tumor detection is based on the performance of the method and should include morphometric information (three axes dimensions, volume) and topographic information (number, location specifying liver segment and lobe/lobes). The specification of these data is important for staging liver tumors and prognosis.
Tumor characterization is a complex process based on a sum of criteria leading towards tumor nature definition. Often, other diagnostic procedures, especially interventional ones are no longer necessary. Tumor characterization using the ultrasound method will be based on the following elements: consistency (solid, liquid, mixed), echogenicity, structure appearance (homogeneous or heterogeneous), delineation from adjacent liver parenchyma (capsular, imprecise), elasticity, posterior acoustic enhancement effect, the relation with neighboring organs or structures (displacement, invasion), vasculature (presence and characteristics on Doppler ultrasonography and contrast-enhanced ultrasound (CEUS).
The substrate on which the tumor condition develops (if the liver is normal or if there is evidence of diffuse liver disease) and the developing context (oncology, septic) are also added. Particular attention should be paid to the analysis of the circulatory bed. Microcirculation investigation allows for discrimination between benign and malignant tumors. Characteristic elements of malignant circulation are vascular density, presence of vessels with irregular paths and size, some of them intercommunicating, some others blocked in the end with "glove finger" appearance, the presence of arterio-arterial and arterio-venous shunts, lack or incompetence of arterial precapillary sphincter made up of smooth musculatures. Diagnosis and characterization of liver tumors require a distinct approach for each group of conditions, using the available procedures discussed above for each of them. The correlation with the medical history, the patient's clinical and functional (biochemical and hematological) status are important elements that should also be considered.
Benign liver tumors Benign liver tumors generally develop on normal or fatty liver, are single or multiple (generally paucilocular), have distinct delineation, with increased echogenity (hemangiomas, benign focal nodular hyperplasia) or absent, with posterior acoustic enhancement effect (cysts), have distinct delineation (hydatid cyst), lack of vascularization or show a characteristic circulatory pattern, displace normal liver structures and even neighboring organs (in case of large sizes), are quite elastic and do not invade liver vessels. The patient has a good general status, as tumors are often asymptomatic, being incidentally discovered.
Liver cysts They can be single or multiple, with variable size, generally less than 20 mm (congenital). Rarely, sizes can reach several centimeters, leading up to the substitution of a whole liver lobe (acquired, parasitic). They may be associated with renal cysts; in this case the disease has a hereditary, autosomal dominant transmission (von Hippel Lindau disease).
The ultrasound appearance is a well defined lesion, with very thin, almost unapparent walls, without circulatory signal at Doppler or CEUS investigation. The content is transonic suggesting fluid composition. The presence of membranes, abundant sediment or cysts inside is suggestive for parasitic, hydatid nature. Posterior from the lesion the acoustic enhancement phenomenon is seen, which strengthens the suspicion of fluid mass. They typically displace normal liver vessels but no vascular or biliary invasion occurs.
Hemangioma
It is the most common liver tumor with a prevalence of 0.4 – 7.4%. It is generally asymptomatic but also can be associated with pain complaints or cytopenia and/or anemia when it is very bulky. It is unique or paucilocular. It can be associated with other types of benign liver tumors. Characteristic 2D ultrasound appearance is that of a very well defined lesion, with sizes of 2–3 cm or less, showing increased echogenity and, when located in contact with the diaphragm, a "mirror image" phenomenon can be seen. When palpating the liver with the transducer the hemangioma is compressible sending reverberations backwards. Doppler exploration reveals no circulatory signal due to very slow flow speed. CEUS investigation has real diagnosis value due to the typical behavior of progressive CA enhancement of the tumor from the periphery towards the center. The enhancement is slow, during several minutes, depending on the size of hemangioma and on the presence (or absence) of internal thrombosis. During late (sinusoidal) phase, if totally "filled" with CA, hemangioma appears isoechoic to the liver. Deviations from the above described behavior can occur in arterialized hemangiomas or those containing arterio-venous shunts. In these cases, differentiation from a malignant tumor is difficult and requires other imaging procedures, follow up and measurements of the tumor at short time intervals.
Focal nodular hyperplasia
It is a tumor developed secondary to a circulatory abnormality with abundant arterial vessels having a characteristic location in the center of the tumor, within a fibrotic scar. A radial vessels network develops from this level with peripheral orientation. The tumor's circulatory bed is rich in microcirculatory and portal venous elements. The incidence is higher in younger women and tumor development is accelerated by oral contraceptives intake. 2D ultrasound appearance is a fairly well-defined mass, with variable sizes, usually single, solid consistency with inhomogeneous structure. Rarely the central scar can be distinguished. Spectral Doppler examination detects central arterial vessels and CFM exploration reveals their radial position. CEUS examination shows central tumor filling of the circulatory bed during arterial phase and completely enhancement during portal venous phase. During this phase the center of the lesion becomes hypoechoic, enhancing the tumor scar. During the late phase the tumor remains isoechoic to the liver, which strengthens the diagnosis of benign lesion.
Adenoma It is a benign tumor made up of normal or atypical hepatocytes. It has an incidence of 0.03%. Its development is induced by intake of anabolic hormones and oral contraceptives. The tumor is asymptomatic but may be associated with right upper quadrant pain in case of internal bleeding. 2D ultrasound shows a well-defined, un-encapsulated, solid mass. It may have a heterogeneous structure in case of intratumoral hemorrhage. Doppler examination shows no circulatory signal. CEUS exploration is quite ambiguous and cannot always establish a differential diagnosis with hepatocellular carcinoma. Thus, during the arterial phase there is a centripetal and inhomogeneous enhancement. During the portal venous phase there is a moderate wash out. During late phase the appearance is isoechoic or hypoechoic, due to lack of Kupffer cells.
Malignant liver tumors Malignant liver tumors develop on cirrhotic liver (hepatocellular carcinoma, HCC) or normal liver (metastases). They are single or multiple (especially metastases), have a variable, generally imprecise delineation, may have a very pronounced circulatory signal (hepatocellular carcinoma and some types of metastases), have a heterogeneous structure (the result of intratumoral circulatory disorders, consequence of hemorrhage or necrosis) and are firm to touch, even rigid. The patient's general status correlates with the underlying disease (vascular and parenchymal decompensation for liver cirrhosis, weight loss, lack of appetite and anemia with cancer).
Hepatocellular carcinoma (HCC) It is the most common liver malignancy. It develops secondary to cirrhosis therefore, ultrasound examination every 6 months combined with alpha fetoprotein (AFP) determination is an effective method for early detection and treatment monitoring for this type of tumor . Clinically, HCC overlaps with advanced liver cirrhosis (long evolution, repeated vascular and parenchymal decompensation, sometimes bleeding due to variceal leakage) in addition to accelerated weight loss in the recent past and lack of appetite.
HCC appearance on 2D ultrasound is that of a solid tumor, with imprecise delineation, with heterogeneous structure, uni- or multilocular (encephaloid form). An "infiltrative" type is also described which is difficult to discriminate from liver nodular reconstruction in cirrhosis. Typically HCC invades liver vessels, primarily the portal veins but also the hepatic veins . Doppler examination detects a high speed arterial flow and low impedance index (correlated with described changes in tumor angiogenesis). The spatial distribution of the vessels is irregular, disordered. CEUS examination shows hyperenhancement of the lesion during the arterial phase. During the portal venous phase there is a specific "wash out" of ultrasound contrast agent (UCA) and the tumor appears hypoechoic during the late phase. Poorly differentiated tumors may have a stronger wash out leading to an isoechoic appearance to the liver parenchyma during portal venous phase. This appearance was found in approx. 30% of cases. The described changes have diagnostic value in liver nodules larger than 2 cm.
Ultrasound is useful in HCC detection, stadialization and assessing therapeutic efficacy. In terms of staging related to therapy effectiveness, the Barcelona classification is used which identifies five HCC stages. Curative therapy is indicated in early stages, which include very early stage (single nodule <2 cm), curable by surgical resection (survival 50-70% five years after surgical resection) and early stage (single nodule of 2–5 cm, or up to 3 nodules <3 cm) which can be treated by radiofrequency ablation (RFA) and liver transplantation. Intermediate stage (polinodular, without portal invasion) and advanced stage (N1, M1, with portal invasion) undergo palliative therapies (TACE and sorafenib systemic therapy) and in the end stage only symptomatic therapy applies.
Cholangiocarcinoma It develops on non cirrhotic liver. 2D ultrasound appearance is uncharacteristic – solid mass with heterogeneous structure, poorly delineated, often with peripheral location and weak Doppler circulation signal. CEUS examination reveals a moderate enhancement of the tumor periphery during arterial phase followed by wash-out during portal venous phase and hypoechoic appearance during late phase.
Liver metastases
US examination is required to detect liver metastases in patients with oncologic history. In addition, the method can incidentally detect metastases in asymptomatic patients. Early identification (small sizes, small number) is important to establish an optimal course of treatment which can be complex (chemotherapy, radiofrequency ablation, surgical resection) but welcomed. In addition, discrimination of synchronous lesions that have a different nature is also important knowing that up to 25–50% of liver lesions less than 2 cm detected in cancer patients may be benign . US sensitivity for metastases detection varies depending on the examiner's experience and the equipment used and ranges between 40 and 80% . Sensitivity is conditioned by the size and acoustic impedance of the nodules. For a lesion diameter below 10 mm US accuracy is greatly reduced, reaching approx. 20%. Other elements contributing to lower US performance are: excessive obesity, fatty liver disease, hypomobility of the diaphragm, and certain patterns of hyperechoic or isoechoic metastases that can be overlooked or can mimic benign conditions. Conventional US appearance of metastases is uncharacteristic, consisting of circumscribed lesions, with clear, imprecise or "halo" delineation, with homogeneous or